This renewal application requests support for the Rochester Epidemiology Project (REP) that has supported the medical records-linkage system for residents of Olmsted County, MN, since 1966. This unique research infrastructure chronicles the medical care delivered to community residents from the early 1900s to the present and has supported population-based epidemiologic investigations of virtually every study design and of most disease entities occurring in the U.S. The REP has supported the work of a large number of investigators at Mayo Medical Center, Olmsted Medical Center, and other academic institutions, and has permitted the efficient conduct of extramurally- funded studies of diseases with substantial societal impact. The REP currently supports 40 government-funded grants, and since its initial funding 42 years ago, more than 1,800 manuscripts have been published in the peer-reviewed literature, including 214 since our last competing renewal in 2005. This extensive data repository from a geographically-defined population is virtually unparalleled in this country, and it is essential that this important research infrastructure be preserved and extended into the future. Each cycle of this grant has presented an opportunity to not only maintain the core medical records-linkage function, but also to enhance its utility. In this renewal application, we propose to update the REP medical records-linkage system through 2015 (Aim 1); to enhance the REP infrastructure by linking additional data on medical services and procedures and their corresponding costs, drug prescriptions, and immunizations (Aim 2); and to expand the REP infrastructure to the larger population of individuals residing in the 8-county region of southeastern Minnesota (Olmsted plus surrounding Dodge, Fillmore, Wabasha, Mower, Goodhue, Winona, and Houston counties; Aim 3). These new aims build on our accomplishments from the current and previous project cycles that include more timely data collection, massive scanning and diagnostic indexing of historical paper medical records, addition of new sources of information and analytic methods, development of an ongoing census enumeration, and development of tools to increase ease of access while providing greater data security. Thus, the aims proposed in this renewal application will provide increased data availability for the growing number of multidisciplinary teams of clinical investigators, epidemiologists, statisticians, and basic scientists who are addressing significant public health questions. The ultimate goal is to continue to support population-based research of disease etiology, preventive interventions, improved medical practice, and better health for the population, as outlined in the NIH Roadmap.